Heart Failure, DiastolicPhase 4NCT07554638
Incretin Therapies in Obesity-related HFpEF
A Phase 4 study testing Tirzepatide in people with Heart Failure, Diastolic and Heart Failure With Preserved Ejection Fraction, run by Columbia University at 1 site in United States.
Trial summary
The central hypothesis to be tested is that patients with obesity and heart failure with preserved ejection fraction (HFpEF) prescribed tirzepatide will demonstrate reductions in measured plasma volume. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction, Obesity
- What is being tested?
- Tirzepatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Aug 2026to Apr 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of heart failure (HF) per the ACC/AHA guidelines with NYHA class II-III symptoms
- Left ventricular ejection fraction >= 45% within 6 months of recruitment
- At least one of the following: elevated N-terminal pro- B-type natriuretic peptide (NT-proBNP) >=200 pg/ml (>=600 pg/ml with concurrent atrial fibrillation), evidence of structural heart disease (left atrial (LA) enlargement with LA volume index >29 mL/m2 or LA diameter >=40 mm in males/>38= mm in females), elevated filling pressures (resting wedge >15 mmHg or exercise wedge >25 mmHg, lateral E/e' ratio >12 or septal E/e' > 15)
- Body mass index (BMI) >30 kg/m2
- Stable doses of HF medications within 4 weeks of screening with optimal volume control in the opinion of the investigator.
Who cannot join
- Acute decompensated HF within 4 weeks of screening
- Major cardiovascular event within 90 days of screening (myocardial infarction, stroke)
- Alternate cause of HFpEF such as cardiac amyloidosis, infiltrative cardiomyopathy, hypertrophic cardiomyopathy, severe valvular disease
- Estimated glomerular fibrilation rate (EGFR) <15 ml/min/1.73m2 or dialysis dependence
- Poorly controlled diabetes (A1c > 9.5%) OR any type 1 diabetes mellitis
- History of acute or chronic pancreatitis
Show all 11Show fewer
- Personal or family history of multiple endocrine neoplasia (MEN) or medullary thyroid cancer
- Clinically significant gastric emptying abnormality
- Medical comorbidities that limit survival
- Inability to comply with the study protocol
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Columbia University Irving Medical Center (CUIMC) / NewYork Presbyterian Hospital (NYP)
New York, New York, 10032
About this study
Official title: Identifying Therapeutic Mechanisms for Incretin-Based Treatment in Obesity-Related Heart Failure With Preserved Ejection Fraction (HFpEF)
The central hypothesis to be tested is that patients with obesity and heart failure with preserved ejection fraction (HFpEF) prescribed tirzepatide will demonstrate reductions in measured plasma volume. In conjunction with state-of-the-art body composition analysis and measures of adipokines, this will establish an important mechanism of clinical benefit and inform disease pathophysiology. To accomplish this, this study will perform a 15-month prospective cohort study in 50 patients with obesity and HFpEF who clinically qualify for treatment with tirzepatide. The investigators will serially measure plasma volume and body composition with quantitative magnetic resonance to determine changes over time with tirzepatide treatment.
Read the detailed description
The prevalence of obesity among United States adults is over 40% and is projected to affect over half the population within the coming decade. Obesity is a strong independent risk factor for the development of heart failure (HF) and specifically the phenotype of heart failure with preserved ejection fraction (HFpEF) of whom 84% have obesity. Accordingly, anti-obesity medications are a major focus of recent clinical investigation in patients with obesity and HFpEF. Randomized controlled trials studying incretin mimetics, including glucagon-like peptide 1 (GLP1) receptor agonist (semaglutide) and GLP1/glucose-dependent insulinotropic (GIP) receptor co-agonists (tirzepatide), have improved clinical outcomes patients with obesity and HFpEF. The mechanisms underlying the clinical benefit remain incompletely understood.
Patients with obesity and HFpEF demonstrate distinct structural and hemodynamic features mediated in part by plasma volume (PV) expansion. A major mechanism responsible for PV expansion in obesity is elevated serum leptin, an adipokine with a concentration directly proportional to fat mass. In excess, leptin activates neurohormonal and sympathetic pathways that result in hyperaldosteronism, perpetuating sodium retention and PV expansion in HFpEF. This leads to distinct echocardiographic and hemodynamic changes reflecting increased cardiac volumes and pressures. Compared to those without obesity, patients with obesity and HFpEF have greater left atrial (LA) dilatation, greater concentric left ventricular (LV) remodeling, greater right ventricular (RV) dysfunction, and elevated resting and exercise intracardiac filling pressures.
Preliminary data from secondary analyses of randomized trial data have shown significant reductions in estimated PV in patients on treatment tirzepatide compared to placebo. These changes were associated with improvements in end organ function, functional capacity, and quality of life. Notably, prediction equations to estimate PV are inaccurate, demonstrating weak correlation with the gold standard dilution technique with radiolabeled iodinated serum albumin. Measuring changes in PV with this method would establish an important mechanism of clinical benefit in this population.
In addition, to further understand this mechanism and inform disease pathophysiology, it is also imperative to understand changes in body composition that occur with incretin-based therapies. Quantitative magnetic resonance (QMR) is a highly precise body composition assessment technique that can estimate fat mass, fat-free (lean) mass, free water and total body water (TBW) over time and has been utilized by the research team in other HFpEF cohorts. The investigators will leverage this technology to demonstrate the association between reductions in fat mass and serum leptin with PV reduction, representing a key pathway in the pathophysiology of obesity and HFpEF. In addition, the impact of incretin mimetics on lean mass in patients with obesity and HFpEF is important to establish given the association between lean mass reduction with sarcopenia and poor outcomes in HFpEF, especially in older adults. Due to biased assessment techniques, prior studies have demonstrated highly variable effects on lean mass.
The following are the Specific Aims of the study:
Specific Aim 1: To measure changes in PV in patients with obesity and HFpEF treated with tirzepatide. Hypothesis 1: Tirzepatide treatment will result in significant reduction in measured PV assessed using the gold standard indicator tracer dilution technique with 131-iodine-labeled albumin.
Specific Aim 2: To elucidate the relationship between changes in fat mass, serum adipokine profile, and PV in patients with obesity and HFpEF on tirzepatide treatment. Hypothesis 2: Reductions in QMR-estimated fat mass and reduction in serum leptin will be associated with significant reduction in measured PV.
Specific Aim 3: To quantify changes in lean mass in patients with obesity and HFpEF on tirzepatide treatment. Hypothesis 3: Treatment with tirzepatide will be associated with significant reduction in lean mass over time estimated with QMR.
Exploratory aim: To determine the impact of measured PV reduction on cardiac structure and quality of life in patients with obesity and HFpEF on tirzepatide therapy.
- Being tested
- Tirzepatide
- Medical subject headings
- Heart Failure, Diastolic, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Also called Mounjaro
Glucagon-like 1 receptor agonist/glucose-dependent insulinotropic polypeptide receptor agonist
| Study group | Role | What they receive |
|---|---|---|
| Tirzepatide | Experimental | After a 3-month control period, participants will be prescribed tirzepatide and undergo serial plasma volume measurement and body composition analysis. Participants will be prescribed tirzepatide under the brand name Monjauro if they have diabetes, and under the brand name Zepbound if they do not have diabetes. All participants will be initiated on an initial dose of 2.5 mg injected subcutaneously in the thigh or abdomen every week on same day and at the same time. Receives: Drug: Tirzepatide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma volume
Plasma volume is measured using 131-iodine labeled serum albumin. The isotope is injected via an intravenous line and serial blood samples are taken and analyzed using the Blood Volume Analyzer-100 to derive the participant's blood volume and plasma volume. This will be performed at serial visits to determine the effect of tirzepatide therapy on measured plasma volume over time.
Measured: 12 months
Secondary outcomes (2)
Fat mass
Body composition analysis will be performed with quantitative magnetic resonance (QMR). QMR will be performed early morning in a fasting state with participants in uniform hospital gowns and socks. Briefly, the QMR system generates a signal that modifies the spin of hydrogen atoms and uses an algorithm to evaluate the resulting T1 and T2 relaxation curves specific to one of the components of body composition: fat mass, fat-free mass, total body water. This will be performed at serial visits to determine the effect of tirzepatide therapy on fat mass over time.
Measured: 12 months
Lean mass
Body composition analysis will be performed with QMR. QMR will be performed early morning in a fasting state with participants in uniform hospital gowns and socks. Briefly, the QMR system generates a signal that modifies the spin of hydrogen atoms and uses an algorithm to evaluate the resulting T1 and T2 relaxation curves specific to one of the components of body composition: fat mass, fat-free mass, total body water. This will be performed at serial visits to determine the effect of tirzepatide therapy on lean mass over time.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2026
- Study start7 Aug 2026
- Primary completionApr 2029 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure, DiastolicStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elissa A. Driggin, MD, Columbia University
- Investigators
- Elissa A Driggin, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07554638
- Sponsor's protocol ID
- AAAV9609
- Status last verified
- Aug 2026
- First submitted
- 21 Apr 2026
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identifying Therapeutic Mechanisms for Incretin-Based Treatment in Obesity-Related Heart Failure With Preserved Ejection Fraction (HFpEF)
- ClinicalTrials.gov ID
- NCT07554638
- Acronym / sponsor ID
- AAAV9609
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 7 Aug 2026 (actual)
- Primary completion
- Apr 2029 (estimated)
- Study completion
- Apr 2030 (estimated)
- First posted
- 28 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The central hypothesis to be tested is that patients with obesity and heart failure with preserved ejection fraction (HFpEF) prescribed tirzepatide will demonstrate reductions in measured plasma volume. In conjunction with state-of-the-art body composition analysis and measures of adipokines, this will establish an important mechanism of clinical benefit and inform disease pathophysiology. To accomplish this, this study will perform a 15-month prospective cohort study in 50 patients with obesity and HFpEF who clinically qualify for treatment with tirzepatide. The investigators will serially measure plasma volume and body composition with quantitative magnetic resonance to determine changes over time with tirzepatide treatment.
Detailed description
The prevalence of obesity among United States adults is over 40% and is projected to affect over half the population within the coming decade. Obesity is a strong independent risk factor for the development of heart failure (HF) and specifically the phenotype of heart failure with preserved ejection fraction (HFpEF) of whom 84% have obesity. Accordingly, anti-obesity medications are a major focus of recent clinical investigation in patients with obesity and HFpEF. Randomized controlled trials studying incretin mimetics, including glucagon-like peptide 1 (GLP1) receptor agonist (semaglutide) and GLP1/glucose-dependent insulinotropic (GIP) receptor co-agonists (tirzepatide), have improved clinical outcomes patients with obesity and HFpEF. The mechanisms underlying the clinical benefit remain incompletely understood.
Patients with obesity and HFpEF demonstrate distinct structural and hemodynamic features mediated in part by plasma volume (PV) expansion. A major mechanism responsible for PV expansion in obesity is elevated serum leptin, an adipokine with a concentration directly proportional to fat mass. In excess, leptin activates neurohormonal and sympathetic pathways that result in hyperaldosteronism, perpetuating sodium retention and PV expansion in HFpEF. This leads to distinct echocardiographic and hemodynamic changes reflecting increased cardiac volumes and pressures. Compared to those without obesity, patients with obesity and HFpEF have greater left atrial (LA) dilatation, greater concentric left ventricular (LV) remodeling, greater right ventricular (RV) dysfunction, and elevated resting and exercise intracardiac filling pressures.
Preliminary data from secondary analyses of randomized trial data have shown significant reductions in estimated PV in patients on treatment tirzepatide compared to placebo. These changes were associated with improvements in end organ function, functional capacity, and quality of life. Notably, prediction equations to estimate PV are inaccurate, demonstrating weak correlation with the gold standard dilution technique with radiolabeled iodinated serum albumin. Measuring changes in PV with this method would establish an important mechanism of clinical benefit in this population.
In addition, to further understand this mechanism and inform disease pathophysiology, it is also imperative to understand changes in body composition that occur with incretin-based therapies. Quantitative magnetic resonance (QMR) is a highly precise body composition assessment technique that can estimate fat mass, fat-free (lean) mass, free water and total body water (TBW) over time and has been utilized by the research team in other HFpEF cohorts. The investigators will leverage this technology to demonstrate the association between reductions in fat mass and serum leptin with PV reduction, representing a key pathway in the pathophysiology of obesity and HFpEF. In addition, the impact of incretin mimetics on lean mass in patients with obesity and HFpEF is important to establish given the association between lean mass reduction with sarcopenia and poor outcomes in HFpEF, especially in older adults. Due to biased assessment techniques, prior studies have demonstrated highly variable effects on lean mass.
The following are the Specific Aims of the study:
Specific Aim 1: To measure changes in PV in patients with obesity and HFpEF treated with tirzepatide. Hypothesis 1: Tirzepatide treatment will result in significant reduction in measured PV assessed using the gold standard indicator tracer dilution technique with 131-iodine-labeled albumin.
Specific Aim 2: To elucidate the relationship between changes in fat mass, serum adipokine profile, and PV in patients with obesity and HFpEF on tirzepatide treatment. Hypothesis 2: Reductions in QMR-estimated fat mass and reduction in serum leptin will be associated with significant reduction in measured PV.
Specific Aim 3: To quantify changes in lean mass in patients with obesity and HFpEF on tirzepatide treatment. Hypothesis 3: Treatment with tirzepatide will be associated with significant reduction in lean mass over time estimated with QMR.
Exploratory aim: To determine the impact of measured PV reduction on cardiac structure and quality of life in patients with obesity and HFpEF on tirzepatide therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tirzepatide | Experimental | Drug: TirzepatideAfter a 3-month control period, participants will be prescribed tirzepatide and undergo serial plasma volume measurement and body composition analysis. Participants will be prescribed tirzepatide under the brand name Monjauro if they have diabetes, and under the brand name Zepbound if they do not have diabetes. All participants will be initiated on an initial dose of 2.5 mg injected subcutaneously in the thigh or abdomen every week on same day and at the same time. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of heart failure (HF) per the ACC/AHA guidelines with NYHA class II-III symptoms
- Left ventricular ejection fraction >= 45% within 6 months of recruitment
- At least one of the following: elevated N-terminal pro- B-type natriuretic peptide (NT-proBNP) >=200 pg/ml (>=600 pg/ml with concurrent atrial fibrillation), evidence of structural heart disease (left atrial (LA) enlargement with LA volume index >29 mL/m2 or LA diameter >=40 mm in males/>38= mm in females), elevated filling pressures (resting wedge >15 mmHg or exercise wedge >25 mmHg, lateral E/e' ratio >12 or septal E/e' > 15)
- Body mass index (BMI) >30 kg/m2
- Stable doses of HF medications within 4 weeks of screening with optimal volume control in the opinion of the investigator.
Key exclusion criteria (11 listed)
- Acute decompensated HF within 4 weeks of screening
- Major cardiovascular event within 90 days of screening (myocardial infarction, stroke)
- Alternate cause of HFpEF such as cardiac amyloidosis, infiltrative cardiomyopathy, hypertrophic cardiomyopathy, severe valvular disease
- Estimated glomerular fibrilation rate (EGFR) <15 ml/min/1.73m2 or dialysis dependence
- Poorly controlled diabetes (A1c > 9.5%) OR any type 1 diabetes mellitis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirzepatideAlso: MounjaroGlucagon-like 1 receptor agonist/glucose-dependent insulinotropic polypeptide receptor agonist | Drug | Tirzepatide |
Primary outcome
Plasma volume
Time frame: 12 months
Plasma volume is measured using 131-iodine labeled serum albumin. The isotope is injected via an intravenous line and serial blood samples are taken and analyzed using the Blood Volume Analyzer-100 to derive the participant's blood volume and plasma volume. This will be performed at serial visits to determine the effect of tirzepatide therapy on measured plasma volume over time.
2 secondary outcomes
Fat mass
Time frame: 12 months
Lean mass
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Elissa A Driggin, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tirzepatide in people with Heart Failure, Diastolic and Heart Failure With Preserved Ejection Fraction, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jessica Idumonyi (212-305-1429, joi2102@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma volume (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.